The present invention relates to a method for producing 4-(2'-methoxyethyl) phenol, or more particularly to a method for producing 4-(2'-methoxyethyl) phenol from 4-hydroxyacetophenone. 4-(2'-methoxyethyl)phenol is useful as an intermediate in the production of Metoprolol which is a beta-adrenergic blocker known as 1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methoxyethyl)amino]-2-propanol. The manufacture of Metroprolol tartrate from 4-(2'-methoxyethyl)phenol is described in the Pharmaceutical Manufacturing Encyclopedia, volume 2, pages 1009-1010 as well as in U.S. Pat. No. 3,873,600, both of which are incorporated herein by reference.
4-(2'-methoxyethyl)phenol is not a new compound. Its production by complex mechanisms is shown in French patent 2,487,338; the Journal of the American Chemical Society, Vol. 85, p. 575 (1963) and the Journal of the American Chemical Society, vol 79, p. 756 (1957). French patent 2,487,338 starts with a brominated alkyloxy phenol which is then treated with a Grignard reagent to produce an organo-magnesium compound. This is then reacted with an aldehyde, acetate or nitrile to produce a secondary alcohol or ketone which is then treated with a mineral acid to produce, in the case closest to this invention, a methoxy-4-hydroxyacetophenone. This ketone is then hydrogenated to produce a carbinol which is then reacted with acetic anhydride and sodium acetate to obtain a vinyl ether. The vinyl ether is then catalytically hydrogenated to produce a methoxyethyl phenylacetate, which is then saponified to obtain 4-(2'-methoxyethyl)phenol. The present invention improves upon this complex procedure by providing the alpha-methoxy-4-hydroxyacetophenone in a technically much more feasible way and by directly and substantially completely hydrogenating alpha-methoxy-4-hydroxyacetophenone. As a general overview the method of this invention proceeds by brominating 4-hydroxyacetophenone, causing a methoxide-bromide exchange and conducting a single step reduction of the methoxy- para-hydroxyacetophenone to 4-(2'-methoxyethyl)phenol according to the reaction scheme: ##STR1##